Is Your Brain Leaking?

A leaky gut may lead to a leaky brain. Here’s how to head it off.

Posted Nov 24, 2020

Recent research has demonstrated a solid link between gut microbes and mental health. There are likely to be multiple mechanisms, but one theory stands above the others: Gut microbes may get unbalanced, like an ecosystem with too many hyenas, and lead to inflammation and even brain damage.

 Scott Anderson
A leaky brain can cause problems.
Source: Scott Anderson

That’s because pathogenic bacteria can eat away at the lining of the gut and create leaks large enough for toxins and even microbes to sneak through into the bloodstream. Once there, the heart obligingly pumps them to every organ in the body. That includes the brain, which is shielded by a cellular fortress that stretches around the blood vessels throughout the skull and spinal cord to keep marauding microbes out. This is called the blood-brain barrier (BBB).

The BBB is porous enough to absorb nutrition yet impermeable enough to exclude pathogens, immune cells, and stray neurotransmitters. This is accomplished by molecules that form tight junctions between cells. When that exclusionary function is damaged, the BBB can be loosely said to be leaky. If your BBB leaks, you could be in for a world of trouble.

Looking at brains

In a recent study, Chris Greene, Nicole Hanley, and Matthew Campbell of Trinity College in Dublin looked at postmortem brains of 45 people with psychiatric disorders and 15 controls. They looked at tissue samples and tracked junction chemicals called claudins and occludins that are involved with maintaining an intact BBB. They saw chemical and visual indicators of a leaky BBB in the brains of those with depression and schizophrenia.

They found that depression was associated with signs of leakiness in the nucleus accumbens, a part of the brain involved with the "reward circuit" that uses the neurotransmitters dopamine and serotonin. Schizophrenia, on the other hand, was associated with signs of leakiness in two other areas: the prefrontal cortex, involved with planning, personality, and social behavior; and the hippocampus, involved with emotional regulation, learning, and memory.

The brain is delicate

Our body is marvelously replaceable. We scrape our knee and the skin grows back. We destroy a bit of liver with each cocktail, but the liver regenerates.

The brain is different. When you lose brain cells, you lose memories and important connections that took a lifetime to acquire. The brain is like no other tissue in the body. That explains why so much care—including the intricate webwork of the BBB—goes into protecting it. And so the research showing that a breach in the BBB is related to mental deficits is both reasonable and ground-breaking. Depression, anxiety, cognitive difficulties, dementia—even Alzheimer’s and Parkinson’s—show a significant association with a leaky BBB, pointing to possible treatments.

A recent study by Chilean researchers Juliana a González-Sanmiguel, Luis Aguayo, and Sebastian Aguayo has laid out the compelling connection between a leaky gut and a leaky brain. They found that gut toxins and inflammation were significantly associated with so-called misfolded proteins found in Alzheimer’s, Parkinson’s, and Creutzfeldt-Jakob diseases. This shows a strong gut-brain correlation but stops short of proving causality.

However, causality has been clearly demonstrated in experiments with mice and rats. Studies by John Kelly, Catherine Stanton, John Cryan, and Ted Dinan at University College Cork in Ireland, showed that transferring fecal matter from depressed people to rats makes the rats act depressed. That not only demonstrates causality (microbes can transmit depression), it also shows causality between different species.

It all comes down to inflammation

When a leaky gut allows pathogens to pass through, the immune system goes on alert and chases them down. But if the leakiness continues, over time the BBB can get worn down. The immune system is not fastidious, and it can directly attack our own cells, further contributing to leakiness. For that reason, the killing cells of the immune system are normally unwelcome in the brain, kept out by the BBB.

If pathogens sneak past the BBB and enter the brain, the immune system will not be far behind. Brain inflammation, or encephalitis, is serious, and can directly lead to foggy thinking, fatigue, and depression. If enough tissue is destroyed, the damage may be irreversible.

Sometimes that inflammation is indirect. Hippocrates, for instance, knew that some cases of radical personality change were related to the liver. As he put it, “Those who are mad on account of bile are vociferous, vicious, and do not keep quiet.” Hippocrates also felt that all diseases start in the gut, and thus knew 2500 years ago about some kind of gut-liver-brain connection. In fact this condition, known as hepatic encephalopathy, is associated with gut pathogens that produce ammonia. Today we know that we can cure this phenomenon with oral antibiotics, highlighting the microbial connection.

Chronic systemic inflammation is the likely culprit behind many diseases, not just in the brain. Heart disease, diabetes, obesity, arthritis, and more are suspected to start with inflammation—and the source is typically the gut. So, as odd as it seems, if you don’t want a leaky brain, make sure you attend to your gut. When it is compromised, it can trigger all sorts of health issues and make you miserable.

What to do

To keep in top mental shape, look to diet and exercise to keep your gut microbes happy. On the diet front, fiber is king. These complex chains of sugar can’t be digested by intestinal acids and enzymes, so they make it all the way to the colon where they feed beneficial gut microbes. Those beneficial microbes, in turn, attack and starve out pathogenic bacteria. Fiber is found mainly in veggies, especially beans, onions, artichokes, and others. Exercise is also surprisingly effective at improving your gut microbiota and the integrity of your gut lining. 

A healthy gut will help to keep your BBB intact. The bottom line is: keep your gut microbes happy and they will keep you happy. They can even keep you feeling younger and smarter. And that might be the best news of this brutish year.


Greene, Chris, Nicole Hanley, and Matthew Campbell. “Blood-Brain Barrier Associated Tight Junction Disruption Is a Hallmark Feature of Major Psychiatric Disorders.” Translational Psychiatry 10, no. 1 (November 2, 2020): 1–10.

González-Sanmiguel, Juliana, Christina M. A. P. Schuh, Carola Muñoz-Montesino, Pamina Contreras-Kallens, Luis G. Aguayo, and Sebastian Aguayo. “Complex Interaction between Resident Microbiota and Misfolded Proteins: Role in Neuroinflammation and Neurodegeneration.” Cells 9, no. 11 (November 13, 2020): 2476.

Kelly, John, Yuliya Borre, Ciarán O’Brien, Elaine Patterson, Sahar El Aidy, Jennifer Deane, Paul Kennedy, et al. “Transferring the Blues: Depression-Associated Gut Microbiota Induces Neurobehavioural Changes in the Rat.” Journal of Psychiatric Research 82 (July 1, 2016).